Mast cells contribute to autoimmune diabetes by releasing interleukin-6 and failing to acquire a tolerogenic IL-10+ phenotype

被引：16

作者：

Betto, Elena ^{[1
,2
]}

Usuelli, Vera ^{[3
]}

Mandelli, Alessandra ^{[3
]}

Badami, Ester ^{[4
]}

Sorini, Chiara ^{[3
]}

Capolla, Sara ^{[1
,2
]}

Danelli, Luca ^{[1
,2
]}

Frossi, Barbara ^{[1
,2
]}

Guarnotta, Carla ^{[5
]}

Ingrao, Sabrina ^{[5
]}

Tripodo, Claudio ^{[5
]}

Pucillo, Carlo ^{[1
,2
]}

Gri, Giorgia ^{[1
,2
]}

Falcone, Marika ^{[1
,2
]}

机构：

[1] Univ Udine, Dept Biomed Sci & Technol, Udine, Italy

[2] Univ Udine, MATI Ctr Excellence, Udine, Italy

[3] Ist Sci San Raffaele, Div Immunol Transplantat & Infect Dis, Expt Diabet Unit, Milan, Italy

[4] ISMETT, Mediterranean Inst Transplantat & Adv Specialized, Palermo, Italy

[5] Univ Palermo, Dept Human Pathol, Palermo, Italy

来源：

CLINICAL IMMUNOLOGY | 2017年 / 178卷

关键词：

Mast cells; Autoimmune diabetes; Interleukin-6; Immune tolerance; Interleukin-10; REGULATORY T-CELLS; BIOBREEDING RAT; MICE; ENCEPHALOMYELITIS; ARTHRITIS; IMMUNITY; ANTIBODY; PROTEIN; BETA; NOD;

D O I：

10.1016/j.clim.2015.12.013

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Mast cells (MCs) are innate immune cells that exert positive and negative immune modulatory functions capable to enhance or limit the intensity and/or duration of adaptive immune responses. Although MCs are crucial to regulate T cell immunity, their action in the pathogenesis of autoimmune diseases is still debated. Here we demonstrate that MCs play a crucial role in T1D pathogenesis so that their selective depletion in conditional MC knockout NOD mice protects them from the disease. MCs of diabetic NOD mice are overly inflammatory and secrete large amounts of IL-6 that favors differentiation of IL-17-secreting T cells at the site of autoimmunity. Moreover, while MCs of control mice acquire an IL-10 + phenotype upon interaction with FoxP3 + Treg cells, MCs of NOD mice do not undergo this tolerogenic differentiation. Our data indicate that overly inflammatory MCs unable to acquire a tolerogenic IL-10 + phenotype contribute to the pathogenesis of autoimmune T1D. 2016 Elsevier Inc. All rights reserved.

引用

页码：29 / 38

页数：10

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